Dr
Frances Edwards graduated in Pharmacology at the
University of Sydney, Australia and received her PhD whilst working at the
Max-Planck Institute in Germany under the Nobel Prize winner, Prof. Bert
Sakmann.

After staying on as a postdoctoral fellow in Sakmann's lab, in 1990
she joined David Colquhoun’s group in Pharmacology at UCL as a Wellcome
European Fellow.

After returning to Australia in 1992 Frances held a Queen
Elizabeth II Research Fellowship at the University of Sydney from 1993 until
1996.

In 1996 she joined the Department of Physiology at UCL. Until 2010 the focus of the Edwards lab was
mechanisms of fast synaptic transmission and the role of dendritic spines in
plasticity using electrophysiology and confocal imaging.

In 2010 the research direction largely
shifted to research on Alzheimer's disease, studying several transgenic mouse
models of human mutations in the amyloid pathway or microtubule-associated
protein tau.

The approaches have expanded to include a range of molecular
biology and immunohistochemical techniques and genetics (in collaboration with
John Hardy).

The effects of rising Ab in
Alzheimer’s disease

Alzheimer’s
disease occurs when the ability to control the laying down and/or retrieval of
memory is disturbed.

We hypothesise that this is related to early damage to one
or more of the pathways that the brain can choose to use for plasticity and
homeostasis.

By comparing synaptic transmission, plasticity and morphology in a
range of mouse models with genes for Alzheimer’s disease or prefrontal
dementia, we aim to find distinct or common deficits in the network that would
decrease the flexibility for change.

By concentrating on early stages of the
disease at the time when cognitive deficits are first detected we hope, in
collaboration with GSK and Eisai, to find useful targets for future drug
development.

Understanding gene expression changes throughout the progression
of pathology in different mice models informs the direction of research.

In collaboration
with the Hardy lab we have undertaken a Genome-wide analysis of gene expression
in 5 mice that are transgenic for genes that cause dementia (and WT mice)
throughout the development of the Alzheimer's disease-like phenotype and in 3
different brain regions.

This gives us an invaluable resource to guide our
electrophysiological, immunohistochemical and molecular biology studies of
these mice.

In addition to the synaptic studies, this has led us into studies
of the immune system and neuronal pentraxins.

Processing of
Memory in Health and Disease: Plasticity and Homeostasis in the Hippocampus

Memory must involve activity-dependent changes in the network of
communication between brain cells.

The hippocampus has long been known to be
involved in the laying down of memory and much work on this field has
concentrated on this area of the brain.

Moreover this is one of the first areas
to show changes in Alzheimer’s disease. Cellular phenomena have been described
by which the communication at individual synapses (the connections between
individual neurones) can be strengthened ('long-term potentiation', LTP) or
weakened ('long-term depression', LTD).

But should the changes in the
hippocampus really last indefinitely? If strengthening or weakening of synapses
in a particular pathway are uncontrolled this could result in imbalance of the
overall output of the neurone so that it fires too fast or insufficiently to
maintain healthy function and processing.

Such imbalances can be very damaging,
not only undermining the intended function of the circuit and so impairing
learning but also resulting in conditions such as epilepsy.

As change in
synaptic strength is integral to the very function of the hippocampus, this
region will be particular vulnerable to such problems.

In order to avoid such
imbalance, the neurones are known to have strong balancing (homeostatic)
mechanisms.

A lot of past work has focused on such homeostasis but generally by
studying the effects of weakening or strengthening all the synapses of the
neurones measured, using pharmacological means.

Instead we directly visualise
changes in the synapses (De Simoni et al., 2006) as specialising in high
resolution electrical recording between individual neurones or recording of
plasticity in the network.

We can thus strengthen or weaken the synapses within
one pathway and study what happens to them and their neighbours over time.

We
particularly take advantage of recent findings which have demonstrated a close
correlation between the strength and the size of individual synapses.

Thus we
combine direct recording of synaptic transmission using patch clamp techniques
in brains slices with measurement of synapse size.

Figure legend: An example of
electrophysiological recording (from Parsley et al., 2007). Unitary evoked
glutamatergic synaptic currents recorded with patch clamp techniques from a
mouse hippocampal CA1 neurone. CA3 axons were stimulated by placing an
electrode extracellularly in the Stratum Radiatum and gradually increasing the
voltage of a short (50 μs) pulse. At 4V a synaptic response is seen putatively
due to stimulation of a single axon. This response stays constant until the
voltage reaches 6V when more axons start to be recruited.

Imaging neurones: GFP mice

Using mice expressing GFP, we are
able to image the changes in dendritic spines under different conditions in
organotypic or acute slices and understand the relation between synaptic
plasticity, morphology and homeostasis.